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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 江伯倫(Bor-Luen Chiang) | |
dc.contributor.author | Yu-Tsan Lin | en |
dc.contributor.author | 林于粲 | zh_TW |
dc.date.accessioned | 2021-06-13T17:28:01Z | - |
dc.date.available | 2004-11-26 | |
dc.date.copyright | 2004-11-26 | |
dc.date.issued | 2004 | |
dc.date.submitted | 2004-11-16 | |
dc.identifier.citation | Abeck D, Mempel M. Staphylococcus aureus colonization in atopic dermatitis and its therapeutic implications. Br J Dermatol 1998;139 Suppl 53:13-16.
Akbar AN, Salmon M. Cellular environments and apoptosis: tissue microenvironments control activated T-cell death. Immunol Today 1997;18:72-76. Akiyama H, Toi Y, Kanzaki H, Tada J, Arata J. Prevalence of producers of enterotoxins and toxic shock syndrome toxin-1 among Staphylococcus aureus strains isolated from atopic dermatitis lesions. Arch Dermatol Res 1996;288:418-420. Aly R, Maibach HI, Shinefield HR. Microbial flora of atopic dermatitis. Arch Dermatol 1977;113:780-782. Aroeira LS, Martinez A. The role of IL-4 in the staphylococcal enterotoxin B-triggered immune response: increased susceptibility to shock and deletion of CD8Vbeta8+ T cells in IL-4 knockout mice. Eur J Immunol 1999;29:1397-1405. Bender BG, Leung SB, Leung DY. Actigraphy assessment of sleep disturbance in patients with atopic dermatitis: an objective life quality measure. J Allergy Clin Immunol 2003;111:598-602. Boguniewicz M, Sampson H, Leung SB, Harbeck R, Leung DY. Effects of cefuroxime axetil on Staphylococcus aureus colonization and superantigen production in atopic dermatitis. J Allergy Clin Immunol 2001;108:651-652. Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998;187:129-134. Brann DW, Hendry LB, Mahesh VB. Emerging diversities in the mechanism of action of steroid hormones. J Steroid Biochem Mol Biol 1995;52:113-133. Bunikowski R, Mielke ME, Skarabis H, Worm M, Anagnostopoulos I, Kolde G, Wahn U, Renz H. Evidence for a disease-promoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis. J Allergy Clin Immunol 2000;105:814-819. Busse WW, Rosenwasser LJ. Mechanisms of asthma. J Allergy Clin Immunol 2003;111:S799-S804. Campbell DE, Kemp AS. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in response to Staphylococcus aureus and staphylococcal superantigen in childhood atopic dermatitis. Clin Exp Immunol 1997;107:392-397. Chan LS, Robinson N, Xu L. Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol 2001;117:977-983. Choi YW, Kotzin B, Herron L, Callahan J, Marrack P, Kappler J. Interaction of Staphylococcus aureus toxin 'superantigens' with human T cells. Proc Natl Acad Sci U S A 1989;86:8941-8945. Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997;326 (Pt 1):1-16. Cookson WO, Moffatt MF. The genetics of atopic dermatitis. Curr Opin Allergy Clin Immunol 2002;2:383-387. Dalton DK, Haynes L, Chu CQ, Swain SL, Wittmer S. Interferon gamma eliminates responding CD4+ T cells during mycobacterial infection by inducing apoptosis of activated CD4+ T cells. J Exp Med 2000;192:117-122. Dhar S, Kanwar AJ, Kaur S, Sharma P, Ganguly NK. Role of bacterial flora in the pathogenesis and management of atopic dermatitis. Indian J Med Res 1992;95:234-238. Drake CG, Kotzin BL. Superantigens: biology, immunology, and potential role in disease. J Clin Immunol 1992;12:149-162. Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 1999;68:383-424. Furue M, Terao H, Moroi Y, Koga T, Kubota Y, Nakayama J, Furukawa F, Tanaka Y, Katayama I, Kinukawa N, Nose Y, Urabe K. Dosage and adverse effects of topical tacrolimus and steroids in daily management of atopic dermatitis. J Dermatol 2004;31:277-283. Grassberger M, Baumruker T, Enz A, Hiestand P, Hultsch T, Kalthoff F, Schuler W, Schulz M, Werner FJ, Winiski A, Wolff B, Zenke G. A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol 1999;141:264-273. Griffiths CE. Ascomycin: an advance in the management of atopic dermatitis. Br J Dermatol 2001;144:679-681. Gupta S. Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci 2001;69:2957-2964. Ha SJ, Lee HJ, Byun DG, Kim JW. Expression of T cell receptor V beta chain in lesional skin of atopic dermatitis. Acta Derm Venereol 1998;78:424-427. Hanifin J, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol 1980;92:44-47. Hanifin JM, Rogge JL. Staphylococcal infections in patients with atopic dermatitis. Arch Dermatol 1977;113:1383-1386. Hauser C, Wuethrich B, Matter L, Wilhelm JA, Sonnabend W, Schopfer K. Staphylococcus aureus skin colonization in atopic dermatitis patients. Dermatologica 1985;170:35-39. Herz U, Bunikowski R, Renz H. Role of T cells in atopic dermatitis. New aspects on the dynamics of cytokine production and the contribution of bacterial superantigens. Int Arch Allergy Immunol 1998;115:179-190. Hildeman DA, Zhu Y, Mitchell TC, Bouillet P, Strasser A, Kappler J, Marrack P. Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim. Immunity 2002a;16:759-767. Hildeman DA, Zhu Y, Mitchell TC, Kappler J, Marrack P. Molecular mechanisms of activated T cell death in vivo. Curr Opin Immunol 2002b;14:354-359. Hoeger PH, Lenz W, Boutonnier A, Fournier JM. Staphylococcal skin colonization in children with atopic dermatitis: prevalence, persistence, and transmission of toxigenic and nontoxigenic strains. J Infect Dis 1992;165:1064-1068. Imai T, Nagira M, Takagi S, Kakizaki M, Nishimura M, Wang J, Gray PW, Matsushima K, Yoshie O. Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 1999;11:81-88. Iskedjian M, Piwko C, Shear NH, Langley RG, Einarson TR. Topical calcineurin inhibitors in the treatment of atopic dermatitis: a meta-analysis of current evidence. Am J Clin Dermatol 2004;5:267-279. Janssen O, Stocker A, Sanzenbacher R, Oberg HH, Siddiqi MA, Kabelitz D. Differential regulation of activation-induced cell death in individual human T cell clones. Int Arch Allergy Immunol 2000;121:183-193. Jujo K, Renz H, Abe J, Gelfand EW, Leung DY. Decreased interferon gamma and increased interleukin-4 production in atopic dermatitis promotes IgE synthesis. J Allergy Clin Immunol 1992;90:323-331. Kabelitz D, Pohl T, Pechhold K. Activation-induced cell death (apoptosis) of mature peripheral T lymphocytes. Immunol Today 1993;14:338-339. Kapp A, Allen BR, Reitamo S. Atopic dermatitis management with tacrolimus ointment (Protopic). J Dermatolog Treat 2003;14:5-16. Kappler J, Kotzin B, Herron L, Gelfand EW, Bigler RD, Boylston A, Carrel S, Posnett DN, Choi Y, Marrack P. V beta-specific stimulation of human T cells by staphylococcal toxins. Science 1989;244:811-813. Kawabe Y, Ochi A. Programmed cell death and extrathymic reduction of Vbeta8+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature 1991;349:245-248. Kim CH, Rott L, Kunkel EJ, Genovese MC, Andrew DP, Wu L, Butcher EC. Rules of chemokine receptor association with T cell polarization in vivo. J Clin Invest 2001;108:1331-1339. Konig B, Neuber K, Konig W. Responsiveness of peripheral blood mononuclear cells from normal and atopic donors to microbial superantigens. Int Arch Allergy Immunol 1995;106:124-133. Kotzin BL. Superantigens and their role in disease. Hosp Pract (Off Ed) 1994;29:59-70. Kotzin BL, Leung DY, Kappler J, Marrack P. Superantigens and their potential role in human disease. Adv Immunol 1993;54:99-166. Krammer PH, Behrmann I, Daniel P, Dhein J, Debatin KM. Regulation of apoptosis in the immune system. Curr Opin Immunol 1994;6:279-289. Laouini D, Kawamoto S, Yalcindag A, Bryce P, Mizoguchi E, Oettgen H, Geha RS. Epicutaneous sensitization with superantigen induces allergic skin inflammation. J Allergy Clin Immunol 2003;112:981-987. Leung DY. Atopic dermatitis and the immune system: the role of superantigens and bacteria. J Am Acad Dermatol 2001;45:S13-S16. Leung DY. Infection in atopic dermatitis. Curr Opin Pediatr 2003a;15:399-404. Leung DY, Bhan AK, Schneeberger EE, Geha RS. Characterization of the mononuclear cell infiltrate in atopic dermatitis using monoclonal antibodies. J Allergy Clin Immunol 1983;71:47-56. Leung DY, Bieber T. Atopic dermatitis. Lancet 2003b;361:151-160. Leung DY, Boguniewicz M. Advances in allergic skin diseases. J Allergy Clin Immunol 2003c;111:S805-S812. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest 2004;113:651-657. Leung DY, Jain N, Leo HL. New concepts in the pathogenesis of atopic dermatitis. Curr Opin Immunol 2003d;15:634-638. Lever R, Hadley K, Downey D, Mackie R. Staphylococcal colonization in atopic dermatitis and the effect of topical mupirocin therapy. Br J Dermatol 1988;119:189-198. Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol 1974;90:525-530. Li XM, Kleiner G, Huang CK, Lee SY, Schofield B, Soter NA, Sampson HA. Murine model of atopic dermatitis associated with food hypersensitivity. J Allergy Clin Immunol 2001;107:693-702. Liu X, Beaty TH, Deindl P, Huang SK, Lau S, Sommerfeld C, Fallin MD, Kao WH, Wahn U, Nickel R. Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study. J Allergy Clin Immunol 2003;112:382-388. Luger TA, Lahfa M, Folster-Holst R, Gulliver WP, Allen R, Molloy S, Barbier N, Paul C, Bos JD. Long-term safety and tolerability of pimecrolimus cream 1% and topical corticosteroids in adults with moderate to severe atopic dermatitis. J Dermatolog Treat 2004;15:169-178. Lynch DH, Ramsdell F, Alderson MR. Fas and FasL in the homeostatic regulation of immune responses. Immunol Today 1995;16:569-574. MacDonald HR, Baschieri S, Lees RK. Clonal expansion precedes anergy and death of V beta 8+ peripheral T cells responding to staphylococcal enterotoxin B in vivo. Eur J Immunol 1991;21:1963-1966. Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science 1990;248:705-711. Marrack P, Kappler J, Mitchell T. Type I interferons keep activated T cells alive. J Exp Med 1999;189:521-530. McFadden JP, Noble WC, Camp RD. Superantigenic exotoxin-secreting potential of staphylococci isolated from atopic eczematous skin. Br J Dermatol 1993;128:631-632. Meurer M, Fartasch M, Albrecht G, Vogt T, Worm M, Ruzicka T, Altmeyer PJ, Schneider D, Weidinger G, Braeutigam M. Long-term efficacy and safety of pimecrolimus cream 1% in adults with moderate atopic dermatitis. Dermatology 2004;208:365-372. Miethke T, Wahl C, Gaus H, Heeg K, Wagner H. Exogenous superantigens acutely trigger distinct levels of peripheral T cell tolerance/immunosuppression: dose-response relationship. Eur J Immunol 1994;24:1893-1902. Mitchell T, Kappler J, Marrack P. Bystander virus infection prolongs activated T cell survival. J Immunol 1999;162:4527-4535. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348-2357. Nakatani T, Kaburagi Y, Shimada Y, Inaoki M, Takehara K, Mukaida N, Sato S. CCR4 memory CD4+ T lymphocytes are increased in peripheral blood and lesional skin from patients with atopic dermatitis. J Allergy Clin Immunol 2001;107:353-358. Neuber K, Loliger C, Kohler I, Ring J. Preferential expression of T-cell receptor V beta-chains in atopic eczema. Acta Derm Venereol 1996;76:214-218. Neuber K, Steinrucke K, Ring J. Staphylococcal enterotoxin B affects in vitro IgE synthesis, interferon-gamma, interleukin-4 and interleukin-5 production in atopic eczema. Int Arch Allergy Immunol 1995;107:179-182. Nghiem P, Pearson G, Langley RG. Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol 2002;46:228-241. Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, Leung DY. Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J Allergy Clin Immunol 2003;112:1195-1202. Novak N, Bieber T, Leung DY. Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol 2003;112:S128-S139. Novelli F, D'Elios MM, Bernabei P, Ozmen L, Rigamonti L, Almerigogna F, Forni G, Del Prete G. Expression and role in apoptosis of the alpha- and beta-chains of the IFN-gamma receptor on human Th1 and Th2 clones. J Immunol 1997;159:206-213. Oberg HH, Lengl-Janssen B, Kabelitz D, Janssen O. Activation-induced T cell death: resistance or susceptibility correlate with cell surface fas ligand expression and T helper phenotype. Cell Immunol 1997;181:93-100. Ono SJ, Nakamura T, Miyazaki D, Ohbayashi M, Dawson M, Toda M. Chemokines: roles in leukocyte development, trafficking, and effector function. J Allergy Clin Immunol 2003;111:1185-1199. Orteu CH, Poulter LW, Rustin MH, Sabin CA, Salmon M, Akbar AN. The role of apoptosis in the resolution of T cell-mediated cutaneous inflammation. J Immunol 1998;161:1619-1629. Orteu CH, Rustin MH, O'Toole E, Sabin C, Salmon M, Poulter LW, Akbar AN. The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema. Clin Exp Immunol 2000;122:150-156. Rajka G. Natural history and clinical manifestations of atopic dermatitis. Clin Rev Allergy 1986;4:3-26. Rajka G, Langeland T. Grading of the severity of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1989;144:13-14. Ramsdell F, Seaman MS, Miller RE, Picha KS, Kennedy MK, Lynch DH. Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death. Int Immunol 1994;6:1545-1553. Reitamo S, Harper J, Bos JD, Cambazard F, Bruijnzeel-Koomen C, Valk P, Smith C, Moss C, Dobozy A, Palatsi R. 0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial. Br J Dermatol 2004;150:554-562. Rellahan BL, Jones LA, Kruisbeek AM, Fry AM, Matis LA. In vivo induction of anergy in peripheral V beta 8+ T cells by staphylococcal enterotoxin B. J Exp Med 1990;172:1091-1100. Romagnani S. Human TH1 and TH2 subsets: doubt no more. Immunol Today 1991;12:256-257. Rosen H. Superantigens. Int J Dermatol 1997;36:14-16. Sallusto F, Lenig D, Mackay CR, Lanzavecchia A. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 1998;187:875-883. Salmon M, Scheel-Toellner D, Huissoon AP, Pilling D, Shamsadeen N, Hyde H, D'Angeac AD, Bacon PA, Emery P, Akbar AN. Inhibition of T cell apoptosis in the rheumatoid synovium. J Clin Invest 1997;99:439-446. Sampson HA. Food allergy. Part 1: Immunopathogenesis and clinical disorders. J Allergy Clin Immunol 1999;103:717-728. Schleimer RP. An overview of glucocorticoid anti-inflammatory actions. Eur J Clin Pharmacol 1993;45 Suppl 1:S3-S7. Schlievert PM. Role of superantigens in human disease. J Infect Dis 1993;167:997-1002. Shah D, Hales J, Cooper D, Camp R. Recognition of pathogenically relevant house dust mite hypersensitivity in adults with atopic dermatitis: a new approach? J Allergy Clin Immunol 2002;109:1012-1018. Skov L, Baadsgaard O. Superantigens. Do they have a role in skin diseases? Arch Dermatol 1995;131:829-832. Skov L, Olsen JV, Giorno R, Schlievert PM, Baadsgaard O, Leung DY. Application of Staphylococcal enterotoxin B on normal and atopic skin induces up-regulation of T cells by a superantigen-mediated mechanism. J Allergy Clin Immunol 2000;105:820-826. Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest 1999;103:1103-1111. Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol 2003;112:S118-S127. Strange P, Skov L, Lisby S, Nielsen PL, Baadsgaard O. Staphylococcal enterotoxin B applied on intact normal and intact atopic skin induces dermatitis. Arch Dermatol 1996;132:27-33. Strasser A, Harris AW, Huang DC, Krammer PH, Cory S. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J 1995;14:6136-6147. Taskapan MO, Kumar P. Role of staphylococcal superantigens in atopic dermatitis: from colonization to inflammation. Ann Allergy Asthma Immunol 2000;84:3-10. Thestrup-Pedersen K. Tacrolimus treatment of atopic eczema/dermatitis syndrome. Curr Opin Allergy Clin Immunol 2003;3:359-362. Van Parijs L, Biuckians A, Abbas AK. Functional roles of Fas and Bcl-2-regulated apoptosis of T lymphocytes. J Immunol 1998a;160:2065-2071. Van Parijs L, Peterson DA, Abbas AK. The Fas/Fas ligand pathway and Bcl-2 regulate T cell responses to model self and foreign antigens. Immunity 1998b;8:265-274. Varadhachary AS, Perdow SN, Hu C, Ramanarayanan M, Salgame P. Differential ability of T cell subsets to undergo activation-induced cell death. Proc Natl Acad Sci U S A 1997;94:5778-5783. Vella AT, Dow S, Potter TA, Kappler J, Marrack P. Cytokine-induced survival of activated T cells in vitro and in vivo. Proc Natl Acad Sci U S A 1998;95:3810-3815. Wakugawa M, Nakamura K, Kakinuma T, Onai N, Matsushima K, Tamaki K. CC chemokine receptor 4 expression on peripheral blood CD4+ T cells reflects disease activity of atopic dermatitis. J Invest Dermatol 2001;117:188-196. Weber AK, Wahn U, Renz H. Superantigen-induced T cell death by apoptosis: analysis on a single cell level and effect of IFN-gamma and IL-4 treatment. Int Arch Allergy Immunol 2000;121:215-223. White J, Herman A, Pullen AM, Kubo R, Kappler JW, Marrack P. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 1989;56:27-35. Willemze R, Graaff-Reitsma CB, Cnossen J, Van Vloten WA, Meijer CJ. Characterization of T-cell subpopulations in skin and peripheral blood of patients with cutaneous T-cell lymphomas and benign inflammatory dermatoses. J Invest Dermatol 1983;80:60-66. Yamamoto J, Adachi Y, Onoue Y, Adachi YS, Okabe Y, Itazawa T, Toyoda M, Seki T, Morohashi M, Matsushima K, Miyawaki T. Differential expression of the chemokine receptors by the Th1- and Th2-type effector populations within circulating CD4+ T cells. J Leukoc Biol 2000;68:568-574. Zachary CB, Allen MH, MacDonald DM. In situ quantification of T-lymphocyte subsets and Langerhans cells in the inflammatory infiltrate of atopic eczema. Br J Dermatol 1985;112:149-156. Zhang X, Brunner T, Carter L, Dutton RW, Rogers P, Bradley L, Sato T, Reed JC, Green D, Swain SL. Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis. J Exp Med 1997;185:1837-1849. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/39417 | - |
dc.description.abstract | 過去文獻顯示,高達95% 的異位性皮膚炎患者的皮膚上有金黃色葡萄球菌的增生與感染。此菌會分泌許多外毒素,其中,以金黃色葡萄球菌腸毒素B為異位性皮膚炎患者皮膚上最常見的金黃色葡萄球菌外毒素。這些金黃色葡萄球菌的外毒素是超級抗原,它們可以穿透皮膚,刺激帶有某些特定的T細胞受體beta鏈變異區 (variable region of beta chain of T cell receptor,TCRVbeta) 的T細胞,造成異位性皮膚炎皮膚過敏性發炎反應的持續與惡化。
本研究的目標,是要探討金黃色葡萄球菌超級抗原造成異位性皮膚炎皮膚過敏性發炎反應之持續與惡化的分子機轉。其特定目的包括 : 1) 比較異位性皮膚炎病人、無異位性皮膚炎的呼吸道過敏病病人、及健康人的血清中金黃色葡萄球菌腸毒素A之特異性IgE抗體與金黃色葡萄球菌腸毒素B之特異性IgE抗體的濃度 ; 2) 探討血清中金黃色葡萄球菌腸毒素A之特異性IgE抗體或金黃色葡萄球菌腸毒素B之特異性IgE抗體的濃度和異位性皮膚炎的臨床嚴重程度或皮膚感染病史之間的相關性 ; 3) 比較異位性皮膚炎病人與健康人的金黃色葡萄球菌腸毒素B反應型 (TCRVbeta3陽性或TCRVbeta12陽性或TCRVbeta17陽性) CD4陽性T細胞,在受到金黃色葡萄球菌腸毒素B的刺激之後,所引起的活化、分裂增殖、細胞激素的製造、趨化激素受體的表現、細胞凋亡、caspase-3的活化、以及抗凋亡蛋白Bcl-2及Bcl-2 mRNA濃度的變化 ; 4) 探討外加介白質-4對健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的細胞凋亡、caspase-3的活化、以及Bcl-2及Bcl-2 mRNA濃度的變化的影響 ; 5) 探討藉由加入抗介白質-4中和抗體來抑制本身製造的介白質-4對異位性皮膚炎病人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的細胞凋亡、caspase-3的活化、以及Bcl-2及Bcl-2 mRNA濃度的變化的影響。 我們以酵素免疫分析法來測定血清中金黃色葡萄球菌腸毒素A之特異性IgE抗體與金黃色葡萄球菌腸毒素B之特異性IgE抗體的濃度。此外,我們以免疫螢光染色法及Annexin V染色法倂流式細胞儀分析與同步定量聚合酶連鎖反應,來分析在有或沒有外加重組介白質-4或抗介白質-4中和抗體的情況下分別給予金黃色葡萄球菌腸毒素B刺激的周邊血單核細胞。 結果發現,和無異位性皮膚炎的呼吸道過敏病病人或健康人比較起來,異位性皮膚炎病人有較高的血清中金黃色葡萄球菌超級抗原之特異性IgE抗體的濃度。血清中金黃色葡萄球菌超級抗原之特異性IgE抗體的濃度和異位性皮膚炎的臨床嚴重程度之間有正相關。這些結果暗示,金黃色葡萄球菌超級抗原是一種過敏原,其會引起異位性皮膚炎病人的B細胞製造功能上有意義的金黃色葡萄球菌超級抗原之特異性IgE抗體。然而,血清中金黃色葡萄球菌超級抗原之特異性IgE抗體的濃度和皮膚感染病史之間並無相關。在CD4陽性T細胞受到金黃色葡萄球菌超級抗原的刺激之後所產生的一連串的反應方面,我們發現,CD4陽性T細胞之活化與分裂增殖的程度,在異位性皮膚炎病人與健康人身上是相似的。然而,金黃色葡萄球菌超級抗原的刺激,在健康人的CD4陽性T細胞,主要是引起干擾素-gamma (第一型T輔助細胞細胞激素) 的製造與趨化激素受體CXCR3陽性細胞的增加,而在異位性皮膚炎病人的CD4陽性T細胞,主要是引起介白質-4 (第二型T輔助細胞細胞激素) 的製造與趨化激素受體CCR4陽性細胞的增加。和健康人比較起來,異位性皮膚炎病人的CD4陽性T細胞比較不容易發生金黃色葡萄球菌超級抗原引起的Bcl-2的減少、caspase-3的活化、及細胞凋亡。此外,外加介白質-4可以抑制健康人的CD4陽性T細胞之金黃色葡萄球菌超級抗原引起的Bcl-2的減少、caspase-3的活化、及細胞凋亡。抑制本身製造的介白質-4可以增加異位性皮膚炎病人的CD4陽性T細胞之金黃色葡萄球菌超級抗原引起的Bcl-2的減少、caspase-3的活化、及細胞凋亡。這些結果暗示,在受到金黃色葡萄球菌超級抗原的刺激之後,異位性皮膚炎病人的CD4陽性T細胞會製造介白質-4,而這些介白質-4可以透過抑制金黃色葡萄球菌超級抗原引起的Bcl-2的減少,來抑制CD4陽性T細胞之金黃色葡萄球菌超級抗原引起的caspase-3的活化與細胞凋亡。這會導致被金黃色葡萄球菌超級抗原活化的T細胞無法被清除,皮膚的過敏性發炎反應也就無法終止。 本研究的結果,可以釐清金黃色葡萄球菌超級抗原造成異位性皮膚炎皮膚過敏性發炎反應之持續與惡化的分子機轉,以助於發展對異位性皮膚炎特定的預防與治療之道。在臨床上的應用,本研究暗示,測定血清中金黃色葡萄球菌超級抗原之特異性IgE抗體的濃度,可以提供重要的訊息,以助於異位性皮膚炎病人的追蹤治療。當異位性皮膚炎的臨床病情惡化或併發皮膚感染時,早期積極地使用抗生素來抑制金黃色葡萄球菌,以避免皮膚的T細胞繼續受到金黃色葡萄球菌超級抗原的刺激,對於異位性皮膚炎病情的控制會很有幫助。 | zh_TW |
dc.description.abstract | The skin of atopic dermatitis (AD) patients exhibits a striking susceptibility to colonization and infection with Staphylococcus aureus, which can secrete various exotoxins including staphylococcal enterotoxin B (SEB) being the most common. These exotoxins are superantigens. They may penetrate the skin barrier, stimulate T cells bearing the specific variable region of beta chain of T cell receptor (TCRVbeta), and contribute to the persistence and exacerbation of allergic skin inflammation in AD.
The objective of this study was to clarify the molecular mechanisms that staphylococcal superantigens (SsAgs) contribute to the persistence and exacerbation of allergic skin inflammation in AD. The specific aims were to 1) compare serum staphylococcal enterotoxin A (SEA)-specific IgE and SEB-specific IgE levels among AD patients, patients with respiratory allergy without AD, and healthy subjects; 2) investigate the correlation between serum SEA-specific IgE or SEB-specific IgE levels and AD severity or previous skin infections; 3) determine whether there are differences between AD patients and healthy subjects in SEB-induced activation, proliferation, cytokine production, chemokine receptor expression, apoptosis, caspase-3 activation, and changes of anti-apoptotic protein Bcl-2 and Bcl-2 mRNA levels of SEB-reactive (TCRVbeta3+ or Vbeta12+ or Vbeta17+) CD4+ T cells; 4) investigate the effect of exogenously added interleukin-4 (IL-4) on SEB-induced apoptosis, caspase-3 activation, and changes of Bcl-2 and Bcl-2 mRNA levels in SEB-reactive CD4+ T cells from healthy subjects; 5) investigate the effect of inhibition of endogenous IL-4 by using anti-IL-4 neutralizing antibodies (Abs) on SEB-induced apoptosis, caspase-3 activation, and changes of Bcl-2 and Bcl-2 mRNA levels in SEB-reactive CD4+ T cells from AD patients. Serum SEA-specific IgE and SEB-specific IgE levels were determined by enzyme immunoassay. By using immunofluorescence and Annexin V staining followed by flow cytometric analysis and real-time polymerase chain reaction, we analyzed peripheral blood mononuclear cells with or without SEB stimulation in the presence or absence of recombinant IL-4 or anti-IL-4 neutralizing Abs. We found that AD patients had higher serum SsAg-specific IgE levels than patients with respiratory allergy without AD and healthy subjects. There were positive correlations between serum SsAg-specific IgE levels and AD severity. These findings suggest that SsAgs play the role of allergens and thus may induce the production of functionally-relevant SsAg-specific IgE Abs in AD patients. However, there was no correlation between serum SsAg-specific IgE levels and previous skin infections. About the sequential responses of CD4+ T cells induced by SsAg stimulation, both activation and proliferation of CD4+ T cells were similar in AD patients and healthy subjects. However, SsAgs induced production of interferon-gamma (type 1 T helper cell (Th1) cytokine) in CD4+ T cells from healthy subjects and IL-4 (type 2 T helper cell (Th2) cytokine) in those from AD patients. SsAgs induced up-regulation of chemokine receptor CXCR3+ cells in CD4+ T cells from healthy subjects and CCR4+ cells in those from AD patients. CD4+ T cells from AD patients were more resistant to SsAg-induced decrease of Bcl-2, caspase-3 activation, and apoptosis than those from healthy subjects. Moreover, exogenously added IL-4 inhibited SsAg-induced decrease of Bcl-2, caspase-3 activation, and apoptosis in CD4+ T cells from healthy subjects. Inhibition of endogenous IL-4 increased SsAg-induced decrease of Bcl-2, caspase-3 activation, and apoptosis in CD4+ T cells from AD patients. These findings suggest that following SsAg stimulation, IL-4 produced by CD4+ T cells in AD patients can inhibit SsAg-induced caspase-3 activation and apoptosis of CD4+ T cells through inhibiting SsAg-induced decrease of Bcl-2. This may impair deletion of SsAg-activated T cells and resolution of allergic skin inflammation. The results of this study may clarify the molecular mechanisms that SsAgs contribute to the persistence and exacerbation of allergic skin inflammation in AD, which is important for exploring the specific therapy and prevention of AD. In clinical application, this study suggests that the determination of serum SsAg-specific IgE levels may provide important information in the follow-up and therapy of AD patients. Early and aggressive antibiotic treatment of skin infection or exacerbated AD to prevent SsAg exposure of skin T cells is helpful to disease control of AD. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T17:28:01Z (GMT). No. of bitstreams: 1 ntu-93-D89421013-1.pdf: 877882 bytes, checksum: 3021b20673768d026d316313f5300209 (MD5) Previous issue date: 2004 | en |
dc.description.tableofcontents | 目 錄 I
1、 中文摘要 1 2、 緒論 4 2.1 背景與文獻回顧 4 2.1.1 異位性皮膚炎的臨床表現與致病機轉 4 2.1.2 第一型、第二型T輔助細胞與趨化激素受體的表現 6 2.1.3 金黃色葡萄球菌超級抗原在異位性皮膚炎致病機轉中扮演的角色 7 2.1.4 超級抗原 8 2.1.5 T細胞被活化後所引起的細胞凋亡 9 2.1.6 T細胞被金黃色葡萄球菌超級抗原活化後所引起的細胞凋亡 10 2.2 本研究之目標及其在醫學上的重要性 10 2.3 本研究之假說與特定目的 11 2.3.1 第一部分的研究 11 2.3.2 第二部分的研究 13 2.3.3 第三部分的研究 15 3、 研究方法與材料 18 3.1 第一部分的研究 18 3.1.1 研究個體的來源及血清收集 18 3.1.2 血清中全部IgE抗體、金黃色葡萄球菌腸毒素A及腸毒素B之特異性IgE抗體的濃度之測定 19 3.1.3 統計分析 19 3.2 第二部分的研究 20 3.2.1 研究個體的來源及全血收集 20 3.2.2 細胞培養與刺激 21 3.2.3 金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞上CD69的表現之偵測 22 3.2.4 金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞細胞內的第一型與第二型T輔助細胞細胞激素之偵測 22 3.2.5 金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞上CXCR3與CCR4的表現之偵測 23 3.2.6 金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞的細胞凋亡之偵測 24 3.2.7 CXCR3陽性CD4陽性T細胞或CCR4陽性CD4陽性T細胞的細胞凋亡之偵測 25 3.2.8 流式細胞儀分析 25 3.2.9 統計分析 25 3.3 第三部分的研究 26 3.3.1 研究個體的來源及全血收集 26 3.3.2 細胞培養與刺激 26 3.3.3 金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞細胞內的活化型caspase-3與Bcl-2之偵測 27 3.3.4 流式細胞儀分析 28 3.3.5 金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞的純化 28 3.3.6 金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞的Bcl-2 mRNA濃度之定量 29 3.3.7 統計分析 30 3.4 倫理考量 31 4、 結果 32 4.1 第一部分的研究 32 4.1.1 異位性皮膚炎病人有較高的血清中金黃色葡萄球菌腸毒素A及腸毒素B之特異性IgE抗體的濃度與陽性率 32 4.1.2 血清中金黃色葡萄球菌腸毒素A及腸毒素B之特異性IgE抗體的濃度與陽性率和異位性皮膚炎的臨床嚴重度有正相關 33 4.1.3 異位性皮膚炎病人血清中金黃色葡萄球菌腸毒素A及腸毒素B之特異性IgE抗體的濃度與陽性率和皮膚感染病史無相關 34 4.2 第二部分的研究 34 4.2.1 金黃色葡萄球菌腸毒素B的刺激對異位性皮膚炎病人與健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞數目的影響無差異 34 4.2.2 異位性皮膚炎病人與健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的活化無差異 35 4.2.3 金黃色葡萄球菌腸毒素B,在健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞引起第一型T輔助細胞細胞激素的製造,而在異位性皮膚炎病人引起第二型T輔助細胞細胞激素的製造 35 4.2.4 金黃色葡萄球菌腸毒素B,在健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞引起CXCR3陽性細胞的增加,而在異位性皮膚炎病人引起CCR4陽性細胞的增加 36 4.2.5 異位性皮膚炎病人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞比較不容易發生金黃色葡萄球菌腸毒素B引起的細胞凋亡 37 4.2.6 外加介白質-4可以抑制健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的細胞凋亡 37 4.2.7 抑制本身製造的介白質-4可以增加異位性皮膚炎病人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的細胞凋亡 38 4.2.8 CCR4陽性CD4陽性T細胞比CXCR3陽性CD4陽性T細胞較不容易發生金黃色葡萄球菌腸毒素B引起的細胞凋亡 39 4.2.9 外加介白質-4可以抑制健康人的CXCR3陽性CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的細胞凋亡 39 4.3 第三部分的研究 40 4.3.1 異位性皮膚炎病人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞比較不容易發生金黃色葡萄球菌腸毒素B引起的caspase-3的活化 40 4.3.2 異位性皮膚炎病人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞比較不容易發生金黃色葡萄球菌腸毒素B引起的Bcl-2及Bcl-2 mRNA的減少 41 4.3.3 外加介白質-4可以抑制健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的caspase-3的活化 43 4.3.4 外加介白質-4可以抑制健康人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的Bcl-2及Bcl-2 mRNA的減少 43 4.3.5 抑制本身製造的介白質-4可以增加異位性皮膚炎病人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的caspase-3的活化 44 4.3.6 抑制本身製造的介白質-4可以增加異位性皮膚炎病人的金黃色葡萄球菌腸毒素B反應型CD4陽性T細胞之金黃色葡萄球菌腸毒素B引起的Bcl-2及Bcl-2 mRNA的減少 45 5、 討論 47 6、 展望 59 6.1 本研究之貢獻 59 6.2 本研究在臨床上的應用 60 6.2.1 血清中金黃色葡萄球菌超級抗原之特異性IgE抗體的濃度之測定 60 6.2.2 早期積極的抗生素治療 61 6.2.3 免疫調節劑藥物的研發 62 6.3 未來進一步研究的方向 63 6.3.1 干擾素- | |
dc.language.iso | zh-TW | |
dc.title | 金黃色葡萄球菌超級抗原造成異位性皮膚炎皮膚過敏性發炎反應之持續與惡化的分子機轉 | zh_TW |
dc.title | Molecular Mechanisms that Staphylococcal Superantigens Contribute to the Persistence and Exacerbation of Allergic Skin Inflammation in Atopic Dermatitis | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 賴振宏,黃璟隆,紀秀華,余家利 | |
dc.subject.keyword | 金黃色葡萄球菌超級抗原,異位性皮膚炎,介白質-4,細胞凋亡, | zh_TW |
dc.subject.keyword | atopic dermatitis,staphylococcal superantigen,interleukin-4,apoptosis, | en |
dc.relation.page | 123 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2004-11-16 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
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